Pub Date : 2025-12-24DOI: 10.1016/j.gene.2025.149986
Ze Yao , Ming Lu , Chunshuang Li , Xiang Li , Hui Shang , Songtao Bie
Ginsenoside Rg1 (Rg1), an active compound in Panax ginseng C. A. Meyer (ginseng), has shown potential to ameliorate age-related cell damage and extend lifespan in multiple model organisms. However, the precise molecular mechanisms of its anti-aging effects remain unclear. In this study, we explore the anti-aging mechanisms of ginsenoside Rg1, focusing on its impact on mitophagy in Saccharomyces cerevisiae. Using propidium iodide staining, we found that Rg1 extends the chronological lifespan (CLS) of yeast cells. Further analyses revealed that Rg1 enhances mitochondrial function and antioxidant capacity in yeast cells by inducing mitophagy. Moreover, RNA-Seq and bioinformatics analyses identified the molecular chaperone SSE1 as a key target of Rg1. SSE1 knockout strain demonstrated that Rg1 enhances mitochondrial function and antioxidant capacity through SSE1-dependent mitophagy, thereby extending cell lifespan. Collectively, we concluded that Rg1 exerts its anti-aging effects through SSE1-mediated mitophagy. This study advances our understanding of Rg1-mediated mitophagy and mitochondrial regulation via SSE1, offering a foundation for the rational design of targeted anti-aging treatments.
{"title":"Ginsenoside Rg1 delays chronological aging in a yeast model via SSE1-Mediated mitophagy","authors":"Ze Yao , Ming Lu , Chunshuang Li , Xiang Li , Hui Shang , Songtao Bie","doi":"10.1016/j.gene.2025.149986","DOIUrl":"10.1016/j.gene.2025.149986","url":null,"abstract":"<div><div>Ginsenoside Rg1 (Rg1), an active compound in <em>Panax ginseng</em> C. A. Meyer (ginseng), has shown potential to ameliorate age-related cell damage and extend lifespan in multiple model organisms. However, the precise molecular mechanisms of its anti-aging effects remain unclear. In this study, we explore the anti-aging mechanisms of ginsenoside Rg1, focusing on its impact on mitophagy in <em>Saccharomyces cerevisiae</em>. Using propidium iodide staining, we found that Rg1 extends the chronological lifespan (CLS) of yeast cells. Further analyses revealed that Rg1 enhances mitochondrial function and antioxidant capacity in yeast cells by inducing mitophagy. Moreover, RNA-Seq and bioinformatics analyses identified the molecular chaperone <em>SSE1</em> as a key target of Rg1. <em>SSE1</em> knockout strain demonstrated that Rg1 enhances mitochondrial function and antioxidant capacity through <em>SSE1</em>-dependent mitophagy, thereby extending cell lifespan. Collectively, we concluded that Rg1 exerts its anti-aging effects through <em>SSE1</em>-mediated mitophagy. This study advances our understanding of Rg1-mediated mitophagy and mitochondrial regulation via <em>SSE1</em>, offering a foundation for the rational design of targeted anti-aging treatments.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"982 ","pages":"Article 149986"},"PeriodicalIF":2.4,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-23DOI: 10.1016/j.gene.2025.149970
Ju Tang , Ying-Feng Hu , Jian-Wen Shao , Zhi-Zhong Li
Phoebe chekiangensis, a nationally protected tree endemic to southeastern China, is of high ecological and economic value but lacks genomic resources for conservation and evolutionary studies. In this study, we assembled its complete organelle genomes, including a circular mitogenome of 864,971 bp and a plastome of 154,460 bp. The mitogenome is enriched in dispersed and simple sequence repeats, consistent with extensive structural rearrangements across Lauraceae, whereas coding regions (over 80 % similarity) remain largely collinear under strong functional constraints. We identified 31 mitochondrial plastid DNA sequences (26,890 bp; 3.11 % of the mitogenome), including five intact plastid protein-coding genes (PCGs) and 14 tRNAs, reflecting frequent plastid-to-mitochondrion transfers that may restore missing tRNAs and enhance genome variability. RNA editing analysis revealed 71 mitochondrial and 13 plastid sites, with cox1 harboring the most, suggesting post-transcriptional modification of respiratory genes that could contribute to stress tolerance. Comparative analyses showed that plastid PCGs evolve faster than mitochondrial PCGs, and atp6 displayed a signal of positive selection, potentially linked to adaptive adjustments in ATP synthase function and respiratory efficiency. Phylogenetic analyses based on organelle genomes confirmed the monophyly of Lauraceae but revealed little topological conflicts, likely reflecting lineage-specific substitution-rate heterogeneity. In conclusion, our results provide new insights into the dynamics of organelle genome evolution and establish valuable genomic resources for the conservation and molecular systematics of P. chekiangensis and Lauraceae.
{"title":"Organelle genome analysis reveals adaptation and conservation in endangered tree Phoebe chekiangensis","authors":"Ju Tang , Ying-Feng Hu , Jian-Wen Shao , Zhi-Zhong Li","doi":"10.1016/j.gene.2025.149970","DOIUrl":"10.1016/j.gene.2025.149970","url":null,"abstract":"<div><div><em>Phoebe chekiangensis</em>, a nationally protected tree endemic to southeastern China, is of high ecological and economic value but lacks genomic resources for conservation and evolutionary studies. In this study, we assembled its complete organelle genomes, including a circular mitogenome of 864,971 bp and a plastome of 154,460 bp. The mitogenome is enriched in dispersed and simple sequence repeats, consistent with extensive structural rearrangements across Lauraceae, whereas coding regions (over 80 % similarity) remain largely collinear under strong functional constraints. We identified 31 mitochondrial plastid DNA sequences (26,890 bp; 3.11 % of the mitogenome), including five intact plastid protein-coding genes (PCGs) and 14 tRNAs, reflecting frequent plastid-to-mitochondrion transfers that may restore missing tRNAs and enhance genome variability. RNA editing analysis revealed 71 mitochondrial and 13 plastid sites, with <em>cox1</em> harboring the most, suggesting post-transcriptional modification of respiratory genes that could contribute to stress tolerance. Comparative analyses showed that plastid PCGs evolve faster than mitochondrial PCGs, and <em>atp6</em> displayed a signal of positive selection, potentially linked to adaptive adjustments in ATP synthase function and respiratory efficiency. Phylogenetic analyses based on organelle genomes confirmed the monophyly of Lauraceae but revealed little topological conflicts, likely reflecting lineage-specific substitution-rate heterogeneity. In conclusion, our results provide new insights into the dynamics of organelle genome evolution and establish valuable genomic resources for the conservation and molecular systematics of <em>P. chekiangensis</em> and Lauraceae.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"982 ","pages":"Article 149970"},"PeriodicalIF":2.4,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145832854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-23DOI: 10.1016/j.gene.2025.149978
Qingqing Wei , Wenhui Li , Guina Cui , Yiliang Xu , Shaorong Gao
Bovine induced pluripotent stem cells (biPSCs), which can be obtained through somatic cells reprogramming have multiple potential applications in human disease, regeneration medicine and biotechnical animal breeding. However, the low reprogramming efficiency and poorly exploration of the mechanism underlying the somatic cells reprogramming in cattle restricted the applications of biPSCs. Here, we reported the transcription factor PR-domain containing protein 14 (PRDM14) was highly expressed in bovine fetal testis and intestine. And the expression of PRDM14 showed the lowest level in bovine embryonic fibroblasts (BEF), increased on day 3 and day 18, and finally reached the highest level in induced pluripotent stem cells (iPSCs) during the reprogramming induced by OCT4, SOX2, KLF4 and MYC (OSKM). In a gain-of-function assay, we showed that PRDM14 was able to enhance the efficiency of reprogramming from BEF in conjunction with bovine OSKM. While, silencing of PRDM14 inhibited the reprogramming efficiency of BEF. The bovine iPSCs derived from OSKM plus PRDM14 displayed normal karyotype, expressed pluripotent markers and could differentiated into three germ layers in vitro. Transcriptome analysis of cells at the early, median and late reprogramming stages revealed that several genes involved in oxidative phosphorylation (OXPHOS) are upregulated on day 3 when OXPHOS burst occurs, while downregulated on day 15 when OXPHOS transmits to glycolysis, by ectopic expression of PRDM14. RT-qPCR and ATP content detection further confirmed that PRDM14 could improve somatic cells reprogramming by enhancing OXPHOS at the early stage. Additionally, forced expression of PRDM14 in OSKM-induced biPSCs showed that it upregulates the expression of key pluripotency gene NANOG but downregulates LIN28, DNA methylation genes DNMT1/3B and DNA demethylation genes TET1/2/3. Altogether, our study uncovers PRDM14 exemplifies a key transcription factor required for the reacquisition of pluripotency in bovine somatic cells and the maintenance of bovine iPSCs identity.
{"title":"PRDM14 promotes the bovine somatic stem cell reprogramming through enhancing oxidative phosphorylation at the initial stage","authors":"Qingqing Wei , Wenhui Li , Guina Cui , Yiliang Xu , Shaorong Gao","doi":"10.1016/j.gene.2025.149978","DOIUrl":"10.1016/j.gene.2025.149978","url":null,"abstract":"<div><div>Bovine induced pluripotent stem cells (biPSCs), which can be obtained through somatic cells reprogramming have multiple potential applications in human disease, regeneration medicine and biotechnical animal breeding. However, the low reprogramming efficiency and poorly exploration of the mechanism underlying the somatic cells reprogramming in cattle restricted the applications of biPSCs. Here, we reported the transcription factor PR-domain containing protein 14 (<em>PRDM14</em>) was highly expressed in bovine fetal testis and intestine. And the expression of <em>PRDM14</em> showed the lowest level in bovine embryonic fibroblasts (BEF), increased on day 3 and day 18, and finally reached the highest level in induced pluripotent stem cells (iPSCs) during the reprogramming induced by <em>OCT4</em>, <em>SOX2</em>, <em>KLF4</em> and <em>MYC</em> (OSKM). In a gain-of-function assay, we showed that <em>PRDM14</em> was able to enhance the efficiency of reprogramming from BEF in conjunction with bovine OSKM. While, silencing of <em>PRDM14</em> inhibited the reprogramming efficiency of BEF. The bovine iPSCs derived from OSKM plus <em>PRDM14</em> displayed normal karyotype, expressed pluripotent markers and could differentiated into three germ layers in vitro. Transcriptome analysis of cells at the early, median and late reprogramming stages revealed that several genes involved in oxidative phosphorylation (OXPHOS) are upregulated on day 3 when OXPHOS burst occurs, while downregulated on day 15 when OXPHOS transmits to glycolysis, by ectopic expression of <em>PRDM14</em>. RT-qPCR and ATP content detection further confirmed that <em>PRDM14</em> could improve somatic cells reprogramming by enhancing OXPHOS at the early stage. Additionally, forced expression of <em>PRDM14</em> in OSKM-induced biPSCs showed that it upregulates the expression of key pluripotency gene <em>NANOG</em> but downregulates <em>LIN28</em>, DNA methylation genes <em>DNMT1</em>/<em>3B</em> and DNA demethylation genes <em>TET1</em>/<em>2</em>/<em>3</em>. Altogether, our study uncovers <em>PRDM14</em> exemplifies a key transcription factor required for the reacquisition of pluripotency in bovine somatic cells and the maintenance of bovine iPSCs identity.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"982 ","pages":"Article 149978"},"PeriodicalIF":2.4,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-19DOI: 10.1016/j.gene.2025.149945
Seyedeh Zahra Mousavi , Masomeh Askari , Ken McElreavey , Anu Bashamboo , Najmeh Salehi , Mandana Rastari , Zeynab Rokhsattalab , Bahram Mohammad Soltani , Mehdi Totonchi
Introduction
Teratozoospermia, characterized by abnormal sperm morphology, is a significant factor contributing to the male infertility. Deubiquitinating enzymes play a crucial role in controlling protein synthesis and degradation during spermatogenesis.
Methods
Whole exome sequencing (WES) and the following insilico analysis were performed to detect the associated variant with asthenoteratozoospermia in a consanguineous Iranian family with two affected brothers.
Results
WES identified a novel candidate hemizygous missense mutation (chrX-132161044 T > G:NM_031907.2:c.1205A > C, p.Asn402Thr) in the catalytic domain of the USP26 (Ubiquitin-Specific Peptidase 26) deubiquitinating enzyme in two affected siblings. The USP26 encodes a testis-specific deubiquitinating enzyme which is necessary for normal spermatogenesis and may influence male fertility. The mutation changes asparagine 402 (N) into threonine (T) and was co-segregated with phenotype in other available family members. In-silico predictions indicate that the N402T change not only leads to the absence of a hydrogen bond between the mutant N402T and F430 residues but also causes a reduction in USP26 protein stability, potentially resulting in defects in USP26 enzymatic activity.
Conclusions
Our findings support a potential role for USP26 variants contributing to asthenoteratozoospermia.
摘要畸形精子症是导致男性不育的重要因素，其特征是精子形态异常。去泛素化酶在控制精子发生过程中蛋白质的合成和降解中起着至关重要的作用。方法：采用全外显子组测序（WES）和以下计算机分析方法检测一个有两个兄弟患病的伊朗近亲家庭中与弱异卵精子症相关的变异。结果：WES鉴定出一种新的候选半合子错义突变（chrX-132161044 T > G:NM_031907.2:c）。1205A > C, p.Asn402Thr)在两个患病兄弟姐妹的USP26（泛素特异性肽酶26）去泛素化酶的催化区域。USP26编码睾丸特异性去泛素化酶，这是正常精子发生所必需的，并可能影响男性生育能力。该突变将天冬酰胺402 (N)转变为苏氨酸(T)，并与其他可用家族成员的表型共分离。硅预测表明，N402T的变化不仅导致突变体N402T和F430残基之间缺乏氢键，而且还导致USP26蛋白稳定性降低，可能导致USP26酶活性缺陷。结论：我们的研究结果支持USP26变异对弱异卵精子症的潜在作用。
{"title":"A novel candidate missense variant in the catalytic domain of USP26 associated with asthenoteratozoospermia","authors":"Seyedeh Zahra Mousavi , Masomeh Askari , Ken McElreavey , Anu Bashamboo , Najmeh Salehi , Mandana Rastari , Zeynab Rokhsattalab , Bahram Mohammad Soltani , Mehdi Totonchi","doi":"10.1016/j.gene.2025.149945","DOIUrl":"10.1016/j.gene.2025.149945","url":null,"abstract":"<div><h3>Introduction</h3><div>Teratozoospermia, characterized by abnormal sperm morphology, is a significant factor contributing to the male infertility. Deubiquitinating enzymes play a crucial role in controlling protein synthesis and degradation during spermatogenesis.</div></div><div><h3>Methods</h3><div>Whole exome sequencing (WES) and the following insilico analysis were performed to detect the associated variant with asthenoteratozoospermia in a consanguineous Iranian family with two affected brothers.</div></div><div><h3>Results</h3><div>WES identified a novel candidate hemizygous missense mutation (chrX-132161044 T > G:NM_031907.2:c.1205A > C, p.Asn402Thr) in the catalytic domain of the <em>USP26</em> (Ubiquitin-Specific Peptidase 26) deubiquitinating enzyme in two affected siblings. The <em>USP26</em> encodes a testis-specific deubiquitinating enzyme which is necessary for normal spermatogenesis and may influence male fertility. The mutation changes asparagine 402 (N) into threonine (T) and was co-segregated with phenotype in other available family members. In-silico predictions indicate that the N402T change not only leads to the absence of <em>a</em> hydrogen bond between the mutant N402T and F430 residues but also causes a reduction in <em>USP26</em> protein stability, potentially resulting in defects in <em>USP26</em> enzymatic activity.</div></div><div><h3>Conclusions</h3><div>Our findings support a potential role for <em>USP26</em> variants contributing to asthenoteratozoospermia.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"982 ","pages":"Article 149945"},"PeriodicalIF":2.4,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-19DOI: 10.1016/j.gene.2025.149969
Xinyang Li , Chong Liu , Haidi Hu
Furin is a calcium-dependent serine endoprotease that activates multiple substrates by cleaving at polybasic motifs, playing a pivotal role in human physiology and pathology. This review summarizes the latest research progress regarding Furin’s extensive involvement in infectious diseases, tumor diseases, cardiovascular diseases, neurodegenerative diseases, metabolic diseases, and autoimmune diseases. This review offers an in-depth analysis of Furin’s dual functions, which include promoting viral entry into host cells, driving oncogenesis via growth factors, metalloproteinases, and the Notch signaling pathway, and maintaining metabolic homeostasis and immune tolerance. Key pathophysiological mechanisms involve the dysfunction of Furin substrate activation in atherosclerosis, hypertension, Alzheimer’s disease, diabetes, and other disorders. The review also highlights the potential value of Furin as a diagnostic and prognostic biomarker and therapeutic target, while pointing out the challenges encountered in developing its inhibitors.
{"title":"The expanding role of Furin in human Disease: A comprehensive review","authors":"Xinyang Li , Chong Liu , Haidi Hu","doi":"10.1016/j.gene.2025.149969","DOIUrl":"10.1016/j.gene.2025.149969","url":null,"abstract":"<div><div>Furin is a calcium-dependent serine endoprotease that activates multiple substrates by cleaving at polybasic motifs, playing a pivotal role in human physiology and pathology. This review summarizes the latest research progress regarding Furin’s extensive involvement in infectious diseases, tumor diseases, cardiovascular diseases, neurodegenerative diseases, metabolic diseases, and autoimmune diseases. This review offers an in-depth analysis of Furin’s dual functions, which include promoting viral entry into host cells, driving oncogenesis via growth factors, metalloproteinases, and the Notch signaling pathway, and maintaining metabolic homeostasis and immune tolerance. Key pathophysiological mechanisms involve the dysfunction of Furin substrate activation in atherosclerosis, hypertension, Alzheimer’s disease, diabetes, and other disorders. The review also highlights the potential value of Furin as a diagnostic and prognostic biomarker and therapeutic target, while pointing out the challenges encountered in developing its inhibitors.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"981 ","pages":"Article 149969"},"PeriodicalIF":2.4,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-17DOI: 10.1016/j.gene.2025.149947
Wei Cui, Cui-Ming Sun, Bao-Cheng Deng, Pei Liu
{"title":"Retraction notice to “Association of polymorphisms in the interleukin-4 gene with response to hepatitis B vaccine and susceptibility to hepatitis B virus infection: a meta-analysis” [Gene 525 (2013) 35–40]","authors":"Wei Cui, Cui-Ming Sun, Bao-Cheng Deng, Pei Liu","doi":"10.1016/j.gene.2025.149947","DOIUrl":"10.1016/j.gene.2025.149947","url":null,"abstract":"","PeriodicalId":12499,"journal":{"name":"Gene","volume":"981 ","pages":"Article 149947"},"PeriodicalIF":2.4,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-17DOI: 10.1016/j.gene.2025.149948
Jian Min Zhang , Xi Jun Cui , Yun Qiang Xia , Sen Guo
{"title":"Retraction notice to “Correlation between TGF-β1-509 C>T polymorphism and risk of digestive tract cancer in a meta-analysis for 21,196 participants” [Gene 505 (2012) 66-74]","authors":"Jian Min Zhang , Xi Jun Cui , Yun Qiang Xia , Sen Guo","doi":"10.1016/j.gene.2025.149948","DOIUrl":"10.1016/j.gene.2025.149948","url":null,"abstract":"","PeriodicalId":12499,"journal":{"name":"Gene","volume":"981 ","pages":"Article 149948"},"PeriodicalIF":2.4,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-17DOI: 10.1016/j.gene.2025.149967
Hongxia Deng , Dong Ye , Shijie Qiu , Shuang Ye , Chongchang Zhou , Shuai Fang , Yuna Zhang , Shanshan Gu
Objective
Laryngeal cancer is one of the most common malignant tumors of the head and neck, with laryngeal squamous cell carcinoma (LSCC) being the most significant pathological type. Transfer RNA-derived fragments (tRFs) fragments have been implicated in tumor progression through diverse regulatory mechanisms. This study examined the diagnostic value and role of tRF-Val-CAC-008 in LSCC.
Methods
Levels of tRF-Val-CAC-008 were quantified in LSCC tissues, plasma, saliva, and cells using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The diagnostic value of tRF-Val-CAC-008 was then assessed using the receiver operating characteristic (ROC) curve. LSCC cells were transfected with mimics or inhibitors of tRF-Val-CAC-008, which increased or decreased its level accordingly. Cell proliferation was evaluated using EdU and the cell counting kit-8 (CCK-8) assays. The level of lactate dehydrogenase (LDH) in LSCC cells was measured using an LDH release assay. Pyroptosis-associated proteins were analyzed by Western blotting (WB).
Results
tRF-Val-CAC-008 exhibited significantly higher expression levels in LSCC tissues, plasma and saliva. This higher expression correlated with its pro-proliferative effects and suppression of pyroptosis observed in vitro. In LSCC cells, tRF-Val-CAC-008 mimics promoted cell proliferation and reduced LDH secretion. The expression of gasdermin E (GSDME) and caspase-3 proteins was also decreased by tRF-Val-CAC-008 mimics, which in turn regulated pyroptosis. The ROC curves suggest that combined plasma and saliva tRF-Val-CAC-008 can serve as a diagnostic marker to distinguish LSCC patients from healthy participants.
Conclusions
The study concluded that tRF-Val-CAC-008 could act as a diagnostic marker for LSCC; it promotes tumor growth by suppressing pyroptosis and promoting cell proliferation.
目的：喉癌是头颈部最常见的恶性肿瘤之一，喉鳞癌（喉鳞癌）是最重要的病理类型。转移rna衍生片段（tRFs）片段通过多种调节机制与肿瘤进展有关。本研究探讨了tRF-Val-CAC-008在LSCC中的诊断价值和作用。方法：采用实时定量逆转录聚合酶链反应（qRT-PCR）技术，定量检测LSCC组织、血浆、唾液和细胞中tRF-Val-CAC-008的水平。然后用受试者工作特征（ROC）曲线评估tRF-Val-CAC-008的诊断价值。用tRF-Val-CAC-008的模拟物或抑制剂转染LSCC细胞，可相应提高或降低其水平。用EdU和细胞计数试剂盒-8 （CCK-8）测定细胞增殖情况。乳酸脱氢酶（LDH）释放法测定LSCC细胞乳酸脱氢酶（LDH）水平。Western blotting （WB）分析热释热相关蛋白。结果：tRF-Val-CAC-008在LSCC组织、血浆和唾液中的表达水平明显升高。这种高表达与体外观察到的促增殖作用和抑制焦亡有关。在LSCC细胞中，tRF-Val-CAC-008模拟促进细胞增殖并减少LDH分泌。tRF-Val-CAC-008模拟物也降低了gasdermin E （GSDME）和caspase-3蛋白的表达，从而调节焦亡。ROC曲线提示血浆和唾液tRF-Val-CAC-008可作为区分LSCC患者和健康受试者的诊断指标。结论：tRF-Val-CAC-008可作为LSCC的诊断标志物；它通过抑制焦亡和促进细胞增殖来促进肿瘤生长。
{"title":"A novel tRNA-derived fragment tRF-Val-CAC-008 as a diagnostic biomarker and pyroptosis regulator in LSCC","authors":"Hongxia Deng , Dong Ye , Shijie Qiu , Shuang Ye , Chongchang Zhou , Shuai Fang , Yuna Zhang , Shanshan Gu","doi":"10.1016/j.gene.2025.149967","DOIUrl":"10.1016/j.gene.2025.149967","url":null,"abstract":"<div><h3>Objective</h3><div>Laryngeal cancer is one of the most common malignant tumors of the head and neck, with laryngeal squamous cell carcinoma (LSCC) being the most significant pathological type. Transfer RNA-derived fragments (tRFs) fragments have been implicated in tumor progression through diverse regulatory mechanisms. This study examined the diagnostic value and role of tRF-Val-CAC-008 in LSCC.</div></div><div><h3>Methods</h3><div>Levels of tRF-Val-CAC-008 were quantified in LSCC tissues, plasma, saliva, and cells using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The diagnostic value of tRF-Val-CAC-008 was then assessed using the receiver operating characteristic (ROC) curve. LSCC cells were transfected with mimics or inhibitors of tRF-Val-CAC-008, which increased or decreased its level accordingly. Cell proliferation was evaluated using EdU and the cell counting kit-8 (CCK-8) assays. The level of lactate dehydrogenase (LDH) in LSCC cells was measured using an LDH release assay. Pyroptosis-associated proteins were analyzed by Western blotting (WB).</div></div><div><h3>Results</h3><div>tRF-Val-CAC-008 exhibited significantly higher expression levels in LSCC tissues, plasma and saliva. This higher expression correlated with its pro-proliferative effects and suppression of pyroptosis observed in vitro. In LSCC cells, tRF-Val-CAC-008 mimics promoted cell proliferation and reduced LDH secretion. The expression of gasdermin E (GSDME) and caspase-3 proteins was also decreased by tRF-Val-CAC-008 mimics, which in turn regulated pyroptosis. The ROC curves suggest that combined plasma and saliva tRF-Val-CAC-008 can serve as a diagnostic marker to distinguish LSCC patients from healthy participants.</div></div><div><h3>Conclusions</h3><div>The study concluded that tRF-Val-CAC-008 could act as a diagnostic marker for LSCC; it promotes tumor growth by suppressing pyroptosis and promoting cell proliferation.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"982 ","pages":"Article 149967"},"PeriodicalIF":2.4,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-17DOI: 10.1016/j.gene.2025.149966
Syed Rahman , Adith S. Arun , Isaac Yi Kim , William K. Oh , Joseph W. Kim , William J. Kim
Prostate cancer (PCa) remains the second leading cause of cancer-related mortality among U.S. men, driven in large part by metastatic castration-resistant prostate cancer (mCRPC) despite initial responses to androgen-receptor (AR)–targeted therapies. Over the last two decades, treatment options for mCRPC have significantly expanded to include novel therapeutic modalities that integrate biomarker-guided patient selection. These biomarker-driven therapies have ushered us into the era of “precision oncology” in prostate cancer care, and we highlight key developments. In light of these promising early results, we also review key opportunities and challenges ahead. Additionally, we share a conceptual roadmap to leverage multi-omics molecular data in the era of Artificial Intelligence/Machine Learning (AI/ML) to accelerate progress in prostate cancer precision medicine. Specifically, we discuss how these tools may help facilitate the development of near-patient preclinical models for prostate cancer to better capture key aspects of prostate cancer tumor biology. We also discuss a potential path toward accelerating translation of laboratory discoveries into clinical practice for PCa patients.
{"title":"Navigating the winding road toward precision prostate cancer care","authors":"Syed Rahman , Adith S. Arun , Isaac Yi Kim , William K. Oh , Joseph W. Kim , William J. Kim","doi":"10.1016/j.gene.2025.149966","DOIUrl":"10.1016/j.gene.2025.149966","url":null,"abstract":"<div><div>Prostate cancer (PCa) remains the second leading cause of cancer-related mortality among U.S. men, driven in large part by metastatic castration-resistant prostate cancer (mCRPC) despite initial responses to androgen-receptor (AR)–targeted therapies. Over the last two decades, treatment options for mCRPC have significantly expanded to include novel therapeutic modalities that integrate biomarker-guided patient selection. These biomarker-driven therapies have ushered us into the era of “precision oncology” in prostate cancer care, and we highlight key developments. In light of these promising early results, we also review key opportunities and challenges ahead. Additionally, we share a conceptual roadmap to leverage multi-omics molecular data in the era of Artificial Intelligence/Machine Learning (AI/ML) to accelerate progress in prostate cancer precision medicine. Specifically, we discuss how these tools may help facilitate the development of near-patient preclinical models for prostate cancer to better capture key aspects of prostate cancer tumor biology. We also discuss a potential path toward accelerating translation of laboratory discoveries into clinical practice for PCa patients.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"984 ","pages":"Article 149966"},"PeriodicalIF":2.4,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-17DOI: 10.1016/j.gene.2025.149968
Wenbo Liu , Cuifang Lu , Bin Yang , Ying Liu , Jie Yan , Tingyu Song , Xiaofei Wang
Aims
This study investigated the therapeutic potential of Trolline, a natural compound, for alleviating high-glucose (HG)-induced vascular endothelial ferroptosis and mitochondrial dysfunction via the cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11) pathway.
Materials and methods
In db/db mice, inflammatory damage; glucose tolerance; and the expression of SLC7A11, glutathione peroxidase 4 (GPX4), and long-chain acyl-CoA synthetase family member 4 (ACSL4) were detected after treatment with Trolline. An HG-induced human microvascular endothelial cell (HMEC-1) injury model was established in vitro. Fe2+ deposition and GSH levels serve as important indicators of ferroptosis. The mitochondrial membrane potential and the cytoskeleton were determined by JC-1 and F-actin staining, respectively. The levels of apoptosis, cell cycle and reactive oxygen species (ROS) were determined by flow cytometry. Oxidative stress levels were assessed by measuring malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. Ferroptosis- and inflammation-related protein expression in HMEC-1 cells was verified by Western blotting.
Results
In vivo experiments revealed that Trolline can lower blood sugar levels, alleviate inflammatory damage, and regulate the expression of ferroptosis-related proteins in db/db mice. In vitro experiments demonstrated that Trolline can alleviate various effects induced by HG. Under HG conditions, Trolline can inhibit apoptosis, reverse the cell cycle arrest in the SubG1 phase, reduce oxidative stress levels and Fe2+ overload, restore mitochondrial function, promote cytoskeletal remodelling, and regulate the expression of ferroptosis-related proteins. Mechanistically, ferroptosis inhibitors (Ferrostatin-1) and Trolline have the same protective effect on HMEC-1 cells in an HG environment. However, overexpression of SLC7A11 led to loss of the inhibitory effect of Trolline on ferroptosis, which confirms that the effect of Trolline is dependent on the SLC7A11-ferroptosis axis.
Conclusion
Trolline can alleviate diabetic vascular damage through SLC7A11-mediated inhibition of ferroptosis, improved mitochondrial function, and reduced oxidative inflammatory damage, providing a basis for the treatment of diabetic vascular complications.
{"title":"Trolline attenuates diabetic vascular injury by regulating SLC7A11-mediated ferroptosis and mitochondrial dysfunction","authors":"Wenbo Liu , Cuifang Lu , Bin Yang , Ying Liu , Jie Yan , Tingyu Song , Xiaofei Wang","doi":"10.1016/j.gene.2025.149968","DOIUrl":"10.1016/j.gene.2025.149968","url":null,"abstract":"<div><h3>Aims</h3><div>This study investigated the therapeutic potential of Trolline, a natural compound, for alleviating high-glucose (HG)-induced vascular endothelial ferroptosis and mitochondrial dysfunction via the cystine/glutamate antiporter solute carrier family 7 member 11 (SLC7A11) pathway.</div></div><div><h3>Materials and methods</h3><div>In db/db mice, inflammatory damage; glucose tolerance; and the expression of SLC7A11, glutathione peroxidase 4 (GPX4), and long-chain acyl-CoA synthetase family member 4 (ACSL4) were detected after treatment with Trolline. An HG-induced human microvascular endothelial cell (HMEC-1) injury model was established in vitro. Fe<sup>2+</sup> deposition and GSH levels serve as important indicators of ferroptosis. The mitochondrial membrane potential and the cytoskeleton were determined by JC-1 and F-actin staining, respectively. The levels of apoptosis, cell cycle and reactive oxygen species (ROS) were determined by flow cytometry. Oxidative stress levels were assessed by measuring malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. Ferroptosis- and inflammation-related protein expression in HMEC-1 cells was verified by Western blotting.</div></div><div><h3>Results</h3><div>In vivo experiments revealed that Trolline can lower blood sugar levels, alleviate inflammatory damage, and regulate the expression of ferroptosis-related proteins in db/db mice. In vitro experiments demonstrated that Trolline can alleviate various effects induced by HG. Under HG conditions, Trolline can inhibit apoptosis, reverse the cell cycle arrest in the SubG1 phase, reduce oxidative stress levels and Fe<sup>2+</sup> overload, restore mitochondrial function, promote cytoskeletal remodelling, and regulate the expression of ferroptosis-related proteins. Mechanistically, ferroptosis inhibitors (Ferrostatin-1) and Trolline have the same protective effect on HMEC-1 cells in an HG environment. However, overexpression of SLC7A11 led to loss of the inhibitory effect of Trolline on ferroptosis, which confirms that the effect of Trolline is dependent on the SLC7A11-ferroptosis axis.</div></div><div><h3>Conclusion</h3><div>Trolline can alleviate diabetic vascular damage through SLC7A11-mediated inhibition of ferroptosis, improved mitochondrial function, and reduced oxidative inflammatory damage, providing a basis for the treatment of diabetic vascular complications.</div></div>","PeriodicalId":12499,"journal":{"name":"Gene","volume":"981 ","pages":"Article 149968"},"PeriodicalIF":2.4,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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